Definition

Heparin-induced thrombocytopenia (HIT) is an acquired hypercoagulable disorder associated with the use of heparin/heparin-like products due to autoantibodies that target platelet factor 4 (PF4) complexes. HIT typically presents with thrombocytopenia or a decrease in platelet count by at least 50% from preexposure baseline after exposure to heparin products. Major complications of HIT consist of arterial and venous thromboembolic events.

Epidemiology

The incidence of HIT ranges from 0.1% to 1.0% in medical and obstetric patients receiving prophylactic/therapeutic unfractionated heparin (UFH) to >1%–5% in patients receiving UFH after cardiothoracic surgery. Patients exposed only to LMWH have a low incidence of HIT. HIT rarely occurs in association with the synthetic pentasaccharide fondaparinux.²²

Etiology

Autoantibodies that bind to PF4/heparin complexes can activate platelets causing thrombocytopenia and lead to clot formation through increased thrombin generation.

Clinical Presentation

• HIT usually develops within 5–14 days of heparin exposure (typical-onset HIT). Exceptions include delayed-onset HIT, which occurs after stopping heparin, and early-onset HIT, starts within 24 hours of heparin exposure in patients with recent exposure to heparin.
• The 4T scoring system (Table 20-3 - 4T Scoring System for Pretest Probability of Heparin-Induced Thrombocytopenia) calculates HIT pretest probability (NPV > 95%).²³
• HIT rarely causes severe thrombocytopenia (platelet count < 20 × 10⁹/L) or bleeding.
• Thromboembolic complications occur in 30%–75% of HIT patients. Thrombosis can precede, be concurrent with, or follow thrombocytopenia.
  • HIT causing venous thrombi at heparin injection sites produces full-thickness skin infarctions, sometimes in the absence of thrombocytopenia.
• HIT can cause systemic allergic responses following an IV bolus of heparin characterized by fever, hypotension, dyspnea, and cardiac arrest.

Diagnostic Testing

• Obtain surveillance platelet counts every 2–3 days during heparin exposure in patients with >1% risk of HIT.
• For suspected HIT, laboratory tests for PF4 antibodies improve diagnostic accuracy.
  • PF4 antibody testing is a sensitive screening test but lacks specificity.
  • Specificity improves when a positive enzyme-linked immunosorbent assay (ELISA) is quantified in optical density (OD) units. The higher the OD, the more likely the patient has HIT.
  • Rapid tests for PF4 antibodies (i.e., latex immunoturbidimetric assays [LIA]) have a lower sensitivity than ELISA (96.8% vs. 100%).
• Two functional assays test for HIT: serotonin release assay (SRA) and heparin-induced platelet activation (HIPA).
  • Both detect PF4 antibodies in patients’ serum that can activate control platelets in the presence of heparin.
  • Both tests have high specificity for HIT but lower sensitivity than PF4 antibody testing.
• For a low clinical probability of HIT, testing for HIT antibodies is not indicated.
• For a moderate to high clinical probability of HIT, PF4 ELISA testing is indicated. A negative PF4 antibody test effectively rules out HIT.
• A positive PF4 antibody test should lead to confirmatory functional testing (SRA or HIPA).